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Open data
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Basic information
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Title | The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex | |||||||||
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Function / homology | ![]() folic acid transmembrane transporter activity / folate:monoatomic anion antiporter activity / methotrexate transport / methotrexate transmembrane transporter activity / folic acid transport / folate transmembrane transport / folate import across plasma membrane / positive regulation of cGAS/STING signaling pathway / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane ...folic acid transmembrane transporter activity / folate:monoatomic anion antiporter activity / methotrexate transport / methotrexate transmembrane transporter activity / folic acid transport / folate transmembrane transport / folate import across plasma membrane / positive regulation of cGAS/STING signaling pathway / cyclic-GMP-AMP transmembrane transporter activity / cyclic-GMP-AMP transmembrane import across plasma membrane / organic anion transport / 2',3'-cyclic GMP-AMP binding / organic anion transmembrane transporter activity / xenobiotic transmembrane transport / Metabolism of folate and pterines / antiporter activity / folic acid binding / xenobiotic transmembrane transporter activity / transport across blood-brain barrier / folic acid metabolic process / female pregnancy / electron transport chain / brush border membrane / basolateral plasma membrane / periplasmic space / electron transfer activity / iron ion binding / apical plasma membrane / heme binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.72 Å | |||||||||
![]() | Zhang Z / Dang Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular mechanism of substrate recognition by folate transporter SLC19A1. Authors: Yu Dang / Dong Zhou / Xiaojuan Du / Hongtu Zhao / Chia-Hsueh Lee / Jing Yang / Yijie Wang / Changdong Qin / Zhenxi Guo / Zhe Zhang / ![]() ![]() Abstract: Folate (vitamin B) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe ...Folate (vitamin B) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe diseases. Notably, mammalian cells lack the ability to de novo synthesize folate but instead rely on its intake from extracellular sources via specific transporters or receptors, among which SLC19A1 is the ubiquitously expressed one in tissues. However, the mechanism of substrate recognition by SLC19A1 remains unclear. Here we report the cryo-EM structures of human SLC19A1 and its complex with 5-methyltetrahydrofolate at 3.5-3.6 Å resolution and elucidate the critical residues for substrate recognition. In particular, we reveal that two variant residues among SLC19 subfamily members designate the specificity for folate. Moreover, we identify intracellular thiamine pyrophosphate as the favorite coupled substrate for folate transport by SLC19A1. Together, this work establishes the molecular basis of substrate recognition by this central folate transporter. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 111.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.7 KB 17.7 KB | Display Display | ![]() |
Images | ![]() | 169.1 KB | ||
Others | ![]() ![]() | 98.5 MB 98.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hikMC ![]() 8hiiC ![]() 8hijC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_34819_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_34819_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex
Entire | Name: The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex |
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Components |
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-Supramolecule #1: The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex
Supramolecule | Name: The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: BRIL-SLC19A1 chimera
Macromolecule | Name: BRIL-SLC19A1 chimera / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 75.110344 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GPSRATADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRHG FDILVGQIDD ALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLSWRHLVC YLCFYGFMAQ IRPGESFITP YLLGPDKNFT REQVTNEITP V LSYSYLAV ...String: GPSRATADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRHG FDILVGQIDD ALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLSWRHLVC YLCFYGFMAQ IRPGESFITP YLLGPDKNFT REQVTNEITP V LSYSYLAV LVPVFLLTDY LRYTPVLLLQ GLSFVSVWLL LLLGHSVAHM QLMELFYSVT MAARIAYSSY IFSLVRPARY QR VAGYSRA AVLLGVFTSS VLGQLLVTVG RVSFSTLNYI SLAFLTFSVV LALFLKRPKR SLFFNRDDRG RCETSASELE RMN PGPGGK LGHALRVACG DSVLARMLRE LGDSLRRPQL RLWSLWWVFN SAGYYLVVYY VHILWNEVDP TTNSARVYNG AADA ASTLL GAITSFAAGF VKIRWARWSK LLIAGVTATQ AGLVFLLAHT RHPSSIWLCY AAFVLFRGSY QFLVPIATFQ IASSL SKEL CALVFGVNTF FATIVKTIIT FIVSDVRGLG LPVRKQFQLY SVYFLILSII YFLGAMLDGL RHCQRGHHPR QPPAQG LRS AAEEKAAQAL SVQDKGLGGL QPAQSPPLSP EDSLGAVGPA SLEQRQSDPY LAQAPAPQAA EFLSPVTTPS PCTLCSA QA SGPEAADETC PQLAVHPPGV SKLGLQCLPS DGVQNVNQSN S |
-Macromolecule #2: Anti-BRIL Fab heavy chain
Macromolecule | Name: Anti-BRIL Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 27.759207 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGWSLILLFL VAVATRVLSE ISEVQLVESG GGLVQPGGSL RLSCAASGFN VVDFSLHWVR QAPGKGLEWV AYISSSSGST SYADSVKGR FTISADTSKN TAYLQMNSLR AEDTAVYYCA RWGYWPGEPW WKAFDYWGQG TLVTVSSAST KGPSVFPLAP S SKSTSGGT ...String: MGWSLILLFL VAVATRVLSE ISEVQLVESG GGLVQPGGSL RLSCAASGFN VVDFSLHWVR QAPGKGLEWV AYISSSSGST SYADSVKGR FTISADTSKN TAYLQMNSLR AEDTAVYYCA RWGYWPGEPW WKAFDYWGQG TLVTVSSAST KGPSVFPLAP S SKSTSGGT AALGCLVKDY FPEPVTVSWN SGALTSGVHT FPAVLQSSGL YSLSSVVTVP SSSLGTQTYI CNVNHKPSNT KV DKKVEPK SCDKSNSLEV LFQ |
-Macromolecule #3: Anti-Fab nanobody
Macromolecule | Name: Anti-Fab nanobody / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 16.673551 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAGSQVQLQE SGGGLVQPGG SLRLSCAASG RTISRYAMSW FRQAPGKERE FVAVARRSGD GAFYADSVQ GRFTVSRDDA KNTVYLQMNS LKPEDTAVYY CAIDSDTFYS GSYDYWGQGT QVTVSSLEHH HHHH |
-Macromolecule #4: Anti-BRIL Fab light chain
Macromolecule | Name: Anti-BRIL Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.575604 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGWSCIILFL VATATGVHSS DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGT DFTLTISSLQ PEDFATYYCQ QYLYYSLVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN F YPREAKVQ ...String: MGWSCIILFL VATATGVHSS DIQMTQSPSS LSASVGDRVT ITCRASQSVS SAVAWYQQKP GKAPKLLIYS ASSLYSGVPS RFSGSRSGT DFTLTISSLQ PEDFATYYCQ QYLYYSLVTF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN F YPREAKVQ WKVDNALQSG NSQESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #5: THIAMINE DIPHOSPHATE
Macromolecule | Name: THIAMINE DIPHOSPHATE / type: ligand / ID: 5 / Number of copies: 1 / Formula: TPP |
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Molecular weight | Theoretical: 425.314 Da |
Chemical component information | ![]() ChemComp-TPP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.72 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 229158 |
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Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: ANGULAR RECONSTITUTION / Software - Name: cryoSPARC |
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: FLEXIBLE FIT |
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Output model | ![]() PDB-8hik: |